Quality-of-life (QoL) as a predictive biomarker in patients with advanced pancreatic cancer (APC) receiving chemotherapy: results from a prospective multicenter phase 2 trial

Purpose

Pancreatic cancer is rapidly fatal with median survival of only 6 months (mo). Quality-of-life (QoL) was analyzed prospectively in a phase 2 study of gemcitabine (G), capecitabine (C) and bevacizumab (B) in APC patients.

Methods

A total of 50 patients with APC received B 15 mg/kg, C 1,300 mg/m² daily for 2 weeks and G 1,000 mg/m² weekly 2 times; cycles were repeated every 21 days. Endpoints: progression free survival (PFS), overall survival (OS) and assessment of QoL prior to each cycle using the European organization for research and treatment of cancer (EORTC) PAN-26 QoL questionnaire. An exact 95% confidence interval (CI) (Clopper-Pearson method) was used to assess rate of improved QoL (defined as >5% decrease in two consecutive scores compared with baseline).

Results

Patient characteristics- Stage IIB/III/IV: 3/5/42; Sex: 28 M/22 F; Median age: 64 years. QoL in patients- improved: 56%, no improvement: 24%; unevaluable: 20%. Median PFS: 5.8 mo, OS: 9.8 mo. QoL improvement rate: 28/40=0.7 (95% CI: 0.53-0.83) in evaluable patients. Using QoL improvement rate, no significant difference was seen in patients with OS ≥6 mo compared to OS <6 mo. However QoL scores at 3 and 6 weeks from start of treatment correlated strongly with ≥6 mo survival (P value 0.0092 and 0.0081, respectively).

Conclusions

Baseline score and change in QoL scores of patients on G, C and B were not predictive of survival ≥6 mo. Post treatment scores at 3 and 6 weeks from start of therapy however, were predictive of survival ≥6 mo suggesting the potential predictive value of this tool for use in future studies.     

Spectrum of cytological findings in patients with neck lymphadenopathy--experience in a tertiary care hospital in Pakistan

Introduction: Lymph adenopathy is of great clinical significance as underlying diseases may range froma treatable infectious etiology to malignant neoplasms. In fact it is also essential to establish that the swellingin question is a lymph node. Fine needle aspiration cytology (FNAC) plays a vital role in solving these issues,nowadays being recognized as a rapid diagnostic technique because of its simplicity, cost effectiveness, earlyavailability of results, accuracy and minimal invasion. FNAC is particularly helpful in the work-up of cervicalmasses and nodules because biopsy of cervical adenopathy should be avoided unless all other diagnostic modalitieshave failed to establish a diagnosis. Objective: To determine the epidemiological and cytomorphological patternsof enlarged neck nodes. Study Design: This retrospective observational study was performed at the Section ofHistopathology, Aga Khan University Hospital (AKUH), Karachi, Pakistan. Materials and Methods: ThreeHundred and seventy seven (377) neck swelling specimens obtained over a period of two and a half yearsregistered from different regions of Pakistan were selected. Data were analyzed using SPSS 17. Results: Of atotal of 377 cases of FNAC performed on neck nodes, the most frequent cause of lymphadenopathy was foundto be tuberculosis with 199 cases (52.7%), followed by reactive lymphoid hyperplasia with 61 cases (16.1%).Metastatic carcinoma was found to be the third most common cause with 33 cases (8.7%). A diagnosis oflymphoproliferative disorder was rendered in 21 cases (5.5%). Acute and chronic non-specific inflammation wasseen in 16 cases (4.2%). In 47 cases (12%) FNAC was inconclusive. Conclusion: In our study, the predominantcause of enlarged neck nodes was tuberculous lymphadenitis, followed by reactive lymphadenitis and malignantneoplasm, especially metastatic carcinoma and lymphoma. FNAC was helpful in establishing the diagnosis inapproximately 98% of the cases.     

Choroidal thickness changes following cataract surgery using swept source optical coherence tomography

Objective

The aim of this study was to assess changes in subfoveal choroidal thickness (SFCT), measured using swept-source optical coherence tomography (SS-OCT), after routine phacoemulsification cataract surgery.

Incidence of endophthalmitis after intravitreal injections at a tertiary care hospital

Objective

To report the incidence of endophthalmitis after the use of intravitreal injection for anti–vascular endothelial growth factor therapy.

Prevalence of TP53 germ line mutations in young Pakistani breast cancer patients

Women from Pakistan and India are more often diagnosed with early-onset breast cancer than Caucasian women. Given that only 12% of Pakistani women diagnosed with breast cancer at or before 30 years of age have previously been shown to harbor germ line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, the genetic causes of the majority of early-onset cases are unexplained. Since germ line mutations in the tumor suppressor gene TP53 predispose women to early-onset breast cancer, we assessed the prevalence of TP53 mutations in 105 early-onset breast cancer patients from Pakistan, who had previously been found to be negative for BRCA1 and BRCA2 germ line mutations. The patient group included 67 women diagnosed with early-onset breast cancer at or before age 30 with no family history of breast or ovarian cancer (EO30NFH group) and 38 women diagnosed with breast cancer at or before age 40 with one or more first- or second-degree relatives with breast or ovarian cancer (EO40FH group). Mutation analysis of the complete TP53 coding region was performed using denaturing high-performance liquid chromatography analysis, followed by DNA sequencing of variant fragments. One deleterious mutation, c.499-500delCA in exon 5, was identified in the 105 breast cancer patients (1%). This mutation is novel in the germ line and has not been described in other populations. It was detected in a 28-year-old patient with no family history of breast or ovarian cancer. This mutation is rare as it was not detected in additional 157 recently recruited non-BRCA1 and non-BRCA2-associated early-onset breast cancer patients. Our findings show that TP53 mutations may account for a minimal portion of early-onset breast cancer in Pakistan.     

Atypical TDP-43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP

We describe an autosomal dominant, multi-generational, amyotrophic lateral sclerosis (ALS) pedigree in which disease co-segregates with a heterozygous p.Y374X nonsense mutation within TDP-43. Mislocalization of TDP-43 and formation of insoluble TDP-43-positive neuronal cytoplasmic inclusions is the hallmark pathology in >95% of ALS patients. Neuropathological examination of the single case for which CNS tissue was available indicated typical TDP-43 pathology within lower motor neurons, but classical TDP-43-positive inclusions were absent from motor cortex. The mutated allele is transcribed and translated in patient fibroblasts and motor cortex tissue, but overall TDP-43 protein expression is reduced compared to wild-type controls. Despite absence of TDP-43-positive inclusions we confirmed deficient TDP-43 splicing function within motor cortex tissue. Furthermore, urea fractionation and mass spectrometry of motor cortex tissue carrying the mutation revealed atypical TDP-43 protein species but not typical C-terminal fragments. We conclude that the p.Y374X mutation underpins a monogenic, fully penetrant form of ALS. Reduced expression of TDP-43 combined with atypical TDP-43 protein species and absent C-terminal fragments extends the molecular phenotypes associated with TDP-43 mutations and with ALS more broadly. Future work will need to include the findings from this pedigree in dissecting the mechanisms of TDP-43-mediated toxicity.     

Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A multicenter placebo-controlled randomized clinical trial

Until now, no specific and effective treatment exists for coronavirus disease 2019 (COVID-19). Since honey and Nigella sativa (HNS) have established antiviral, antibacterial, antiinflammatory, antioxidant, and immunomodulatory properties, we tested their efficacy for this disease in a multicenter, placebo-controlled, and randomized clinical trial at four medical care facilities in Pakistan. RT-PCR confirmed COVID-19 adults showing moderate or severe disease were enrolled in the trial. Patients were randomly assigned in a 1:1 ratio to receive either honey (1 g kg⁻¹ day⁻¹) and Nigella sativa seeds (80 mg kg⁻¹ day⁻¹) or a placebo for up to 13 days along with standard care. The outcomes included symptoms' alleviation, viral clearance, and 30-day mortality in the intention-to-treat population. Three hundred and thirteen patients, 210 with moderate and 103 with severe disease, underwent randomization from April 30 to July 29, 2020. Among the moderate cases, 107 were assigned to HNS, whereas 103 were assigned to the placebo group. Among the severe cases, 50 were given HNS, and 53 were given the placebo. HNS resulted in ~50% reduction in time taken to alleviate symptoms as compared to placebo (moderate cases: 4 vs. 7 days, Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23–8.84, p < 0.0001 and for severe cases: 6 vs. 13 days, HR: 4.04; 95% CI: 2.46–6.64; p < 0.0001). HNS also cleared the virus earlier than placebo in both moderate cases (6 vs. 10 days, HR: 5.53; 95% CI: 3.76–8.14, p < 0.0001) and severe cases (8.5 vs. 12 days, HR: 4.32; 95% CI: 2.62–7.13, p < 0.0001). HNS further led to a better clinical score on day 6 with normal activity resumption in 63.6% vs. 10.9% among moderate cases (OR: 0.07; 95% CI: 0.03–0.13, p < 0.0001) and hospital discharge in 50% versus 2.8% in severe cases (OR: 0.03; 95% CI: 0.01–0.09, p < 0.0001). In severe cases, the mortality rate was less than 1/4th in the HNS group than in placebo (4% vs. 18.87%, OR: 0.18; 95% CI: 0.02–0.92, p = 0.029). No HNS-related adverse effects were observed. HNS, compared with placebo, significantly improved symptoms, expedited viral load clearance, and reduced mortality in COVID-19 patients. This trial was registered on April 15, 2020 with ClinicalTrials.gov Identifier: NCT04347382.